Spleen cells from Mr1-1pr mice gradually develop a loss of L3T4+ T helper cell function that is age-dependent which is concomitant with the appearance of anti-DNA antibodies and of suppressor cells that selectively suppress only L3T4+ T helper cell function. This observation contrasts with Mr1 +/+ mice that exhibit none of the above during the same time period. Similar results were observed in the (NZBxNZW)F1 autoimmune strain. Human patients with SLE exhibit a similar selective loss of CD4 T helper cell function.